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BAY 1075553 PET-CT for Staging and Restaging Prostate Cancer Patients: Comparison with [18F] Fluorocholine PET-CT (Phase I Study)

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Abstract

Purpose

(2RS,4S)-2-[18F]Fluoro-4-phosphonomethyl-pentanedioic acid (BAY1075553) shows increased uptake in prostate cancer cells. We compared the diagnostic potential of positron emission tomography (PET)-X-ray computed tomography (CT) imaging using BAY1075553 versus [18F]f luorocholine (FCH) PET-CT.

Procedures

Twelve prostate cancer patients (nine staging, three re-staging) were included. The mean prostate-specific antigen in the primary staging and re-staging groups was 21.5 ± 12 and 73.6 ± 33 ng/ml, respectively. Gleason score ranged from 5–9. In nine patients imaged for pre-operative staging, the median Gleason score was 8 (range, 7–9). PET acquisition started with dynamic PET images in the pelvic region followed by static whole-body acquisition. The patients were monitored for 5–8 days afterward for adverse events.

Results

There were no relevant changes in laboratory values or physical examination. Urinary bladder wall received the largest dose equivalent 0.12 mSv/MBq. The whole-body mean effective dose was 0.015 mSv/MBq. There was a significant correlation between detected prostatic lesions by the two imaging modalities (Kappa = 0.356, P < 0.001) and no significant difference in sensitivity (P = 0.16) and specificity (P = 0.41). The sensitivity and specificity of PET imaging using BAY1075553 for lymph node (LN) staging was 42.9 % and 100 %, while it was 81.2 % and 50 % using FCH. The two modalities were closely correlated regarding detection of LNs and bone metastases, although BAY1075553 failed to detect a bone marrow metastasis. Degenerative bone lesions often displayed intense uptake of BAY1075553.

Conclusions

BAY1075553 PET-CT produced no adverse effects, was well tolerated, and detected primary and metastatic prostate cancer. FCH PET-CT results were superior, however, with respect to detecting LN and bone marrow metastases.

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References

  1. Jemal A, Siegel R, Ward E et al (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249

    Article  PubMed  Google Scholar 

  2. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J et al (2012) Cancer incidence and mortality patterns in Europe: estimates for 40 countries. Eur J Cancer 49:1374–1403

    Article  Google Scholar 

  3. Jadvar H (2009) Molecular imaging of prostate cancer with 18F-fluorodeoxyglucose PET. Nat Rev Urol 6:317–323

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Beheshti M, Haim S, Zakavi R et al (2013) Impact of 18F -choline PET/CT in prostate cancer patients with biochemical recurrence: influence of androgen deprivation therapy and correlation with PSA kinetics. J Nucl Med 54:833–840

    Article  CAS  PubMed  Google Scholar 

  5. Beheshti M, Imamovic L, Broinger G et al (2010) 18F choline PET/CT in the preoperative staging of prostate cancer in patients with intermediate or high risk of extracapsular disease: a prospective study of 130 patients. Radiology 254:925–933

    Article  PubMed  Google Scholar 

  6. Dehdashti F, Picus J, Michalski JM et al (2005) Positron tomographic assessment of androgen receptors in prostatic carcinoma. Eur J Nucl Med Mol Imaging 32:344–350

    Article  PubMed  Google Scholar 

  7. Kato T, Tsukamoto E, Kuge Y et al (2002) Accumulation of [11C]acetate in normal prostate and benign prostatic hyperplasia: comparison with prostate cancer. Eur J Nucl Med Mol Imaging 29:1492–1495

    Article  CAS  PubMed  Google Scholar 

  8. Schuster DM, Savir-Baruch B, Nieh PT et al (2011) Detection of recurrent prostate carcinoma with anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid PET/CT and 111In-capromab pendetide SPECT/CT. Radiology 259:852–861

    Article  PubMed Central  PubMed  Google Scholar 

  9. Beheshti M, Langsteger W, Fogelman I (2009) Prostate cancer: role of SPECT and PET in imaging bone metastases. Semin Nucl Med 39:396–407

    Article  PubMed  Google Scholar 

  10. Wright GL Jr, Haley C, Beckett ML, Schellhammer PF (1995) Expression of prostate-specific membrane antigen in normal, benign, and malignant prostate tissues. Urol Oncol 1:18–28

    Article  PubMed  Google Scholar 

  11. Bostwick DG, Pacelli A, Blute M et al (1998) Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer 82:2256–2261

    Article  CAS  PubMed  Google Scholar 

  12. Minner S, Wittmer C, Graefen M et al (2011) High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 71:281–288

    Article  PubMed  Google Scholar 

  13. Mhawech-Fauceglia P, Zhang S, Terracciano L et al (2007) Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using multiple tumour tissue microarray technique. Histopathology 50:472–483

    Article  CAS  PubMed  Google Scholar 

  14. Silver DA, Pellicer I, Fair WR et al (1997) Prostate-specific membrane antigen expression in normal and malignant human tissues. Clin Cancer Res 3:81–85

    CAS  PubMed  Google Scholar 

  15. Chang SS, Reuter VE, Heston WD et al (1999) Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res 59:3192–3198

    CAS  PubMed  Google Scholar 

  16. Sacha P, Zamecnik J, Barinka C et al (2007) Expression of glutamate carboxypeptidase II in human brain. Neuroscience 144:1361–1372

    Article  CAS  PubMed  Google Scholar 

  17. Barrett JA, Coleman RE, Goldsmith SJ et al (2013) First-in-man evaluation of 2 high-affinity PSMA-avid small molecules for imaging prostate cancer. J Nucl Med 54:380–387

    Article  CAS  PubMed  Google Scholar 

  18. Afshar-Oromieh A, Malcher A, Eder M et al (2013) PET imaging with a [68Ga]gallium-labelled PSMA ligand for the diagnosis of prostate cancer: biodistribution in humans and first evaluation of tumour lesions. Eur J Nucl Med Mol Imaging 40:486–495

    Article  CAS  PubMed  Google Scholar 

  19. Troyer JK, Beckett ML, Wright GL Jr (1995) Detection and characterization of the prostate-specific membrane antigen (PSMA) in tissue extracts and body fluids. Int J Cancer 62:552–558

    Article  CAS  PubMed  Google Scholar 

  20. Galsky MD, Eisenberger M, Moore-Cooper S et al (2008) Phase I trial of the prostate-specific membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer. J Clin Oncol 26:2147–2154

    Article  CAS  PubMed  Google Scholar 

  21. Milowsky MI, Nanus DM, Kostakoglu L et al (2004) Phase I trial of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer. J Clin Oncol 22:2522–2531

    Article  CAS  PubMed  Google Scholar 

  22. Osborne JR, Green DA, Spratt DE et al (2014) A prospective pilot study of Zr-J591/prostate specific membrane antigen positron emission tomography in men with localized prostate cancer undergoing radical prostatectomy. J Urol 191(5):1439–1445

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Elsasser-Beile U, Reischl G, Wiehr S et al (2009) PET imaging of prostate cancer xenografts with a highly specific antibody against the prostate-specific membrane antigen. J Nucl Med 50:606–611

    Article  PubMed  Google Scholar 

  24. Lesche R, Kettschau G, Gromov AV et al (2014) Preclinical evaluation of BAY 1075553, a novel (18)F-labelled inhibitor of prostate-specific membrane antigen for PET imaging of prostate cancer. Eur J Nucl Med Mol Imaging 41:89–101

    Article  CAS  PubMed  Google Scholar 

  25. DeGrado TR, Reiman RE, Price DT et al (2002) Pharmacokinetics and radiation dosimetry of 18F-fluorocholine. J Nucl Med 43:92–96

    CAS  PubMed  Google Scholar 

  26. Cimitan M, Bortolus R, Morassut S et al (2006) [(18)F] Fluorocholine PET/CT imaging for the detection of recurrent prostate cancer at PSA relapse: experience in 100 consecutive patients. Eur J Nucl Med Mol Imaging 33:1387–1398

    Article  PubMed  Google Scholar 

  27. Schmid DT, John H, Zweifel R et al (2005) Fluorocholine PET/CT in patients with prostate cancer: initial experience. Radiology 235:623–628

    Article  PubMed  Google Scholar 

  28. Li Y, Cozzi PJ, Russell PJ (2010) Promising tumor-associated antigens for future prostate cancer therapy. Med Res Rev 30:67–101

    PubMed  Google Scholar 

  29. Kallioniemi OP, Wagner U, Kononen J, Sauter G (2001) Tissue microarray technology for high-throughput molecular profiling of cancer. Hum Mol Genet 10:657–662

    Article  CAS  PubMed  Google Scholar 

  30. Liu H, Rajasekaran AK, Moy P et al (1998) Constitutive and antibody-induced internalization of prostate-specific membrane antigen. Cancer Res 58:4055–4060

    CAS  PubMed  Google Scholar 

  31. Ross JS, Sheehan CE, Fisher HA et al (2003) Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer. Clin Cancer Res 9:6357–6362

    CAS  PubMed  Google Scholar 

  32. Perner S, Hofer MD, Kim R et al (2007) Prostate-specific membrane antigen expression as a predictor of prostate cancer progression. Hum Pathol 38:696–701

    Article  CAS  PubMed  Google Scholar 

  33. Mease RC, Foss CA, Pomper MG (2013) PET imaging in prostate cancer: focus on prostate-specific membrane antigen. Curr Top Med Chem 13:951–962

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  34. Nedrow-Byers JR, Jabbes M, Jewett C et al (2012) A phosphoramidate-based prostate-specific membrane antigen-targeted SPECT agent. Prostate 72:904–912

    Article  CAS  PubMed  Google Scholar 

  35. Schafer M, Bauder-Wust U, Leotta K et al (2012) A dimerized urea-based inhibitor of the prostate-specific membrane antigen for 68Ga-PET imaging of prostate cancer. EJNMMI Res 2:23

    Article  PubMed Central  PubMed  Google Scholar 

  36. Banerjee SR, Pullambhatla M, Byun Y et al (2008) 68Ga-labeled inhibitors of prostate-specific membrane antigen (PSMA) for imaging prostate cancer. J Med Chem 53:5333–5341

    Article  Google Scholar 

  37. Chen Y, Foss CA, Byun Y et al (2008) Radiohalogenated prostate-specific membrane antigen (PSMA)-based ureas as imaging agents for prostate cancer. J Med Chem 51:7933–7943

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Maresca KP, Hillier SM, Femia FJ et al (2009) A series of halogenated heterodimeric inhibitors of prostate specific membrane antigen (PSMA) as radiolabeled probes for targeting prostate cancer. J Med Chem 52:347–357

    Article  CAS  PubMed  Google Scholar 

  39. Lapi SE, Wahnishe H, Pham D et al (2009) Assessment of an 18F-labeled phosphoramidate peptidomimetic as a new prostate-specific membrane antigen-targeted imaging agent for prostate cancer. J Nucl Med 50:2042–2048

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Mease RC, Dusich CL, Foss CA et al (2008) N-[N-[(S)-1,3-Dicarboxypropyl]carbamoyl]-4-[18F]fluorobenzyl-l-cysteine, [18F] DCFBC: a new imaging probe for prostate cancer. Clin Cancer Res 14:3036–3043

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Hillier SM, Kern AM, Maresca KP et al (2011) 123I-MIP-1072, a small-molecule inhibitor of prostate-specific membrane antigen, is effective at monitoring tumor response to taxane therapy. J Nucl Med 52:1087–1093

    Article  CAS  PubMed  Google Scholar 

  42. Conti M (2009) State of the art and challenges of time-of-flight PET. Phys Med 25:1–11

    Article  PubMed  Google Scholar 

  43. Moses WW (2007) Recent advances and future advances in time-of-flight PET. Nucl Inst Methods Phys Res A 580:919–924

    Article  CAS  Google Scholar 

  44. Ananias HJ, van den Heuvel MC, Helfrich W, de Jong IJ (2009) Expression of the gastrin-releasing peptide receptor, the prostate stem cell antigen and the prostate-specific membrane antigen in lymph node and bone metastases of prostate cancer. Prostate 69:1101–1108

    Article  PubMed  Google Scholar 

  45. Foss CA, Mease RC, Fan H et al (2005) Radiolabeled small-molecule ligands for prostate-specific membrane antigen: in vivo imaging in experimental models of prostate cancer. Clin Cancer Res 11:4022–4028

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

Piramal Imaging GmbH GmbH, Berlin, Germany, gave financial supported to this study.

Conflict of Interest

A. Stephens and L. Dinkelborg are employees of Piramal Imaging GmbH, Berlin, Germany. Other authors have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine and Endocrinology, PET-CT Center Linz, St. Vincent’s Hospital, Seilerstaette 4, Linz, 4020, Austria

    Mohsen Beheshti, Silke Haim, Christian Schiller & Werner Langsteger

  2. Department of Urology, Prostate Center Linz, St. Vincent’s Hospital, Linz, Austria

    Thomas Kunit & Wolfgang Loidl

  3. Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Rasoul Zakavi

  4. Piramal Imaging GmbH, Berlin, Germany

    Andrew Stephens & Ludger Dinkelborg

  5. Department of Urology, Paracelsus Medical University, Salzburg, Austria

    Thomas Kunit

Authors
  1. Mohsen Beheshti
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Correspondence to Mohsen Beheshti.

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Beheshti, M., Kunit, T., Haim, S. et al. BAY 1075553 PET-CT for Staging and Restaging Prostate Cancer Patients: Comparison with [18F] Fluorocholine PET-CT (Phase I Study). Mol Imaging Biol 17, 424–433 (2015). https://doi.org/10.1007/s11307-014-0800-x

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  • DOI: https://doi.org/10.1007/s11307-014-0800-x

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